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Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma

We have developed the CD44v6-targeting human bivalent antibody fragment AbD19384, an engineered recombinant human bivalent Fab antibody formed via dimerization of dHLX (synthetic double helix loop helix motif) domains, for potential use in antibody-based molecular imaging of squamous cell carcinoma...

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Autores principales: HAYLOCK, ANNA-KARIN, SPIEGELBERG, DIANA, MORTENSEN, ANJA C., SELVARAJU, RAM K., NILVEBRANT, JOHAN, ERIKSSON, OLOF, TOLMACHEV, VLADIMIR, NESTOR, MARIKA V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725455/
https://www.ncbi.nlm.nih.gov/pubmed/26676731
http://dx.doi.org/10.3892/ijo.2015.3290
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author HAYLOCK, ANNA-KARIN
SPIEGELBERG, DIANA
MORTENSEN, ANJA C.
SELVARAJU, RAM K.
NILVEBRANT, JOHAN
ERIKSSON, OLOF
TOLMACHEV, VLADIMIR
NESTOR, MARIKA V.
author_facet HAYLOCK, ANNA-KARIN
SPIEGELBERG, DIANA
MORTENSEN, ANJA C.
SELVARAJU, RAM K.
NILVEBRANT, JOHAN
ERIKSSON, OLOF
TOLMACHEV, VLADIMIR
NESTOR, MARIKA V.
author_sort HAYLOCK, ANNA-KARIN
collection PubMed
description We have developed the CD44v6-targeting human bivalent antibody fragment AbD19384, an engineered recombinant human bivalent Fab antibody formed via dimerization of dHLX (synthetic double helix loop helix motif) domains, for potential use in antibody-based molecular imaging of squamous cell carcinoma in the head and neck region. This is a unique construct that has, to the best of our knowledge, never been assessed for molecular imaging in vivo before. The objective of the present study was to evaluate for the first time the in vitro and in vivo binding properties of radio-iodinated AbD19384, and to assess its utility as a targeting agent for molecular imaging of CD44v6-expressing tumors. Antigen specificity and binding properties were assessed in vitro. In vivo specificity and biodistribution of (125)I-AbD19384 were next evaluated in tumor-bearing mice using a dual-tumor setup. Finally, AbD19384 was labeled with (124)I, and its imaging properties were assessed by small animal PET/CT in tumor bearing mice, and compared with 2-deoxy-2-[18F]fluoro-D-glucose ((18)F-FDG). In vitro studies demonstrated CD44v6-specific binding with slow off-rate for AbD19384. A favorable biodis-tribution profile was seen in vivo, with tumor-specific uptake. Small animal PET/CT images of (124)I-AbD19384 supported the results through clearly visible high CD44v6-expressing tumors and faintly visible low expressing tumors, with superior imaging properties compared to (18)F-FDG. Tumor-to-blood ratios increased with time for the conjugate (assessed up to 72 h p.i.), although 48 h p.i. proved best for imaging. Biodistribution and small-animal PET studies demonstrated that the recombinant Fab-dHLX construct AbD19384 is a promising tracer for imaging of CD44v6 antigen expression in vivo, with the future aim to be used for individualized diagnosis and early detection of squamous cell carcinomas in the head and neck region. Furthermore, this proof-of-concept research established the feasibility of using recombinant Fab-dHLX constructs for in vivo imaging of tumor biomarkers.
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spelling pubmed-47254552016-01-31 Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma HAYLOCK, ANNA-KARIN SPIEGELBERG, DIANA MORTENSEN, ANJA C. SELVARAJU, RAM K. NILVEBRANT, JOHAN ERIKSSON, OLOF TOLMACHEV, VLADIMIR NESTOR, MARIKA V. Int J Oncol Articles We have developed the CD44v6-targeting human bivalent antibody fragment AbD19384, an engineered recombinant human bivalent Fab antibody formed via dimerization of dHLX (synthetic double helix loop helix motif) domains, for potential use in antibody-based molecular imaging of squamous cell carcinoma in the head and neck region. This is a unique construct that has, to the best of our knowledge, never been assessed for molecular imaging in vivo before. The objective of the present study was to evaluate for the first time the in vitro and in vivo binding properties of radio-iodinated AbD19384, and to assess its utility as a targeting agent for molecular imaging of CD44v6-expressing tumors. Antigen specificity and binding properties were assessed in vitro. In vivo specificity and biodistribution of (125)I-AbD19384 were next evaluated in tumor-bearing mice using a dual-tumor setup. Finally, AbD19384 was labeled with (124)I, and its imaging properties were assessed by small animal PET/CT in tumor bearing mice, and compared with 2-deoxy-2-[18F]fluoro-D-glucose ((18)F-FDG). In vitro studies demonstrated CD44v6-specific binding with slow off-rate for AbD19384. A favorable biodis-tribution profile was seen in vivo, with tumor-specific uptake. Small animal PET/CT images of (124)I-AbD19384 supported the results through clearly visible high CD44v6-expressing tumors and faintly visible low expressing tumors, with superior imaging properties compared to (18)F-FDG. Tumor-to-blood ratios increased with time for the conjugate (assessed up to 72 h p.i.), although 48 h p.i. proved best for imaging. Biodistribution and small-animal PET studies demonstrated that the recombinant Fab-dHLX construct AbD19384 is a promising tracer for imaging of CD44v6 antigen expression in vivo, with the future aim to be used for individualized diagnosis and early detection of squamous cell carcinomas in the head and neck region. Furthermore, this proof-of-concept research established the feasibility of using recombinant Fab-dHLX constructs for in vivo imaging of tumor biomarkers. D.A. Spandidos 2015-12-14 /pmc/articles/PMC4725455/ /pubmed/26676731 http://dx.doi.org/10.3892/ijo.2015.3290 Text en Copyright: © Haylock et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
HAYLOCK, ANNA-KARIN
SPIEGELBERG, DIANA
MORTENSEN, ANJA C.
SELVARAJU, RAM K.
NILVEBRANT, JOHAN
ERIKSSON, OLOF
TOLMACHEV, VLADIMIR
NESTOR, MARIKA V.
Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma
title Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma
title_full Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma
title_fullStr Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma
title_full_unstemmed Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma
title_short Evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of CD44v6-expressing squamous cell carcinoma
title_sort evaluation of a novel type of imaging probe based on a recombinant bivalent mini-antibody construct for detection of cd44v6-expressing squamous cell carcinoma
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725455/
https://www.ncbi.nlm.nih.gov/pubmed/26676731
http://dx.doi.org/10.3892/ijo.2015.3290
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